反应详情

温度

60 °C

To a solution of Intermediate A1D (6.61 g, 34.2 mmol) N,O-dimethylhydroxylamine hydrochloride (10.01 g, 103 mmol), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.87 g, 41.1 mmol) and 1-hydroxybenzotriazole hydrate (6.29 g, 41.1 mmol) in 50 ml of DMF was added triethylamine (19.07 mL, 137 mmol). The reaction solution was stirred at 60° C. overnight and then cooled to room temperature. The reaction mixture was partitioned between water and ethyl acetate and transferred to a separatory funnel and washed with 10% LiCl, water, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to provide a dark oil. The crude product mixture was purified via silica gel chromatography (hexanes/EtOAc) to give Intermediate A1E (5.2 g, 22.01 mmol, 64.3% yield). HPLC: RT=1.975 min (H2O/MeOH with TFA, SunFire C18 3.5 μm, 2.1×30 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=237.12 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ 7.17 (dd, J=8.0, 1.2 Hz, 1H), 7.02 (dd, J=7.9, 1.3 Hz, 1H), 6.67 (t, J=7.9 Hz, 1H), 4.78 (br. s., 2H), 3.88-3.73 (m, 1H), 3.69-3.56 (m, 3H), 3.36 (s, 3H), 0.92-0.72 (m, 4H)).

1. temperaturecooled to room temperature
2. customThe reaction mixture was partitioned between water and ethyl acetate
3. customtransferred to a separatory funnel
4. washwashed with 10% LiCl, water, and brine
5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto provide a dark oil
9. customThe crude product mixture was purified via silica gel chromatography (hexanes/EtOAc)
10. customto give Intermediate A1E (5.2 g, 22.01 mmol, 64.3% yield)